CPNE4

Chr 3

copine 4

Also known as: COPN4, CPN4

NCBI Gene: 131034 ENSG00000196353 UniProt: Q96A23 OMIM: 604208

This gene belongs to the highly conserved copine family. It encodes a calcium-dependent, phospholipid-binding protein, which may be involved in membrane trafficking, mitogenesis and development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.47

Clinical Summary— CPNE4

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

41 VUS of 57 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.086

Z-score 3.78

OE 0.26 (0.15–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.65Z-score

OE missense 0.58 (0.51–0.66)

184 obs / 316.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.15–0.47)

0≤0.351.4

Missense OE?0.58 (0.51–0.66)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 8 / 30.5Missense obs/exp: 184 / 316.6Syn Z: -0.50

This gene — mechanism propensity

0.7131th %ile

GOF

0.75top 25%

LOF

0.3454th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

57 submitted variants in ClinVar

ClinVar

Classification Summary

VUS41

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	41	0	41
Likely Benign	0	1	1
Benign	0	0	0
Total	41	1	42

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

12 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap CPNE4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →